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For Your Patients-Multiple Sclerosis

A Rehab Therapy Used in Stroke Recovery May Help in MS

Fitzgerald, Susan

doi: 10.1097/01.NT.0000538940.77583.d7
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In two paired studies, researchers said constraint-induced movement therapy led to improvements in real-world function and white matter integrity on brain scans of patients with multiple sclerosis.

Multiple sclerosis patients (MS) who do a rehabilitation intervention called constraint-induced movement therapy (CIMT) achieved greater use of their more affected arm and also showed more improvement in white matter integrity on brain scans than patients doing other therapeutic activities, two new studies published in tandem in the March issue of Neurorehabilitation and Neural Repair found.

The positive trends were still evident at one year, suggesting that undergoing CIMT for a short period, just 10 days in all, may have a persistent payoff for MS patients experiencing diminished use of an arm.

Previous research has shown that CIMT can be a productive rehabilitation technique for stroke and cerebral palsy, but its usefulness for progressive neurological diseases such as MS has not been fully explored. The new randomized, controlled trial, conducted at the University of Alabama at Birmingham (UAB), is small, but the researchers concluded the results were promising enough to warrant additional study.

The findings appear in a pair of articles, one looking at real-world function and the other at white matter integrity. “These results suggest that CIMT can increase real-world use of the more affected arm in patients with MS for at least one year,” concluded the first article. The second one concluded “the findings suggest in preliminary fashion that the adverse changes in white matter integrity induced by MS might be reversed by CIMT.”

While the articles present an upbeat picture of the potential for CIMT to boost the everyday function of MS patients, a rehabilitation researcher not connected to the studies urged some caution, noting that the study design and methodologies raise questions that need to be addressed.





“I think this needs to be further explored,” said Steven Wolf, PhD, PT, professor in the departments of rehabilitation medicine and cell biology at Emory University School of Medicine in Atlanta. (He is associate editor of the journal but did not review the papers.)

Previous clinical trials have demonstrated that various forms of exercise can benefit MS, but the studies tended to be short, usually under six months, and not particularly focused on whether what was learned in the rehabilitation clinic was effectively transferred to everyday life.

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This new phase 2 study, funded by the National Institutes of Health and the National Multiple Sclerosis Society, involved 20 adults with hemiparetic MS who were assigned to either 35 hours of CIMT or what was characterized as complementary alternative medicine (CAM).

The CIMT intervention, done over 10 consecutive weekdays, had several components: intensive training with the more affected arm on movements and activities of functional significance for three hours a day with rest periods as needed; training with “behavioral shaping,” which involves approaching motor goals in small increments with encouragement to improve on personal best performance and positive feedback at each step; restraint of the less-affected hand with a padded mitt for about 90 percent of waking hours; and a set of behavioral procedures, called the “transfer package,” to facilitate the transfer of the gains in the clinic to the real world.

The transfer package included a behavioral contract; homework practice assignments; keeping an activity diary; and a 30-minute daily interview with the therapist that included administering the Motor Activity Log (MAL) — a scripted interview to assess what was done relative to pre-treatment — a review of the diary, and problem-solving discussions to overcome perceived barriers to arm use.

The control group, also under the supervision of a physical therapist, did activities such as aquatic therapy, gentle yoga, and relaxation techniques like meditation and breathing.

The main clinical outcome was a change on the arm use score on MAL from pretreatment to the one-year mark. All 20 participants completed the active phase of the trial and eight patients in each group were available for the final analysis.

The mean change in MAL for the CIMT group was 2.7 at the one-year mark (1.7/5 improving to 4.4/5), compared to a 0.5 change for the other group (1.6 improving to 2.1). The researchers said a change of 1.0 is considered clinically meaningful. They said that overall “all of the CIMT patients but only three of the CAM patients had clinically meaningful motor improvement at both post-treatment and one-year follow-up.” The CIMT group also had better scores on another standardized test, the Wolf Motor Function Test (named after Dr. Wolf).

The researchers wrote that the findings “suggest that the neuropathology of MS does not preclude long-term real-world functional improvement that is comparable to the responses of other nonprogressive neurologically debilitating illnesses (stroke, traumatic brain injury) in response to the same form of efficacious motor rehabilitation.”

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In the second part of the study, the researchers assessed whether CIMT could induce changes in white matter integrity in MS patients. They noted in background material that other rehabilitation techniques have been found to do so. They analyzed the 20 participants' white matter brain structure using magnetic resonance imaging (MRI), specifically T1-weighted scans and whole-brain diffusion-tensor scans.

“We observed significant pre-to post-treatment white matter improvements for the CIMT group but not the CAM group,” the researchers reported. They identified positive changes in white matter integrity in the corticospinal tract and in temporal, callosal, and visual areas of the brain. They reported that the positive changes were observed within the two weeks that CIMT therapy was administered, which they said was a relatively brief period but consistent with what has been observed in studies involving experimental monkeys.

Study investigator Edward Taub, PhD, professor of psychology at UAB and a pioneer of CIMT, said the “transfer package” portion of the CIMT protocol seems to be key.

“The important part is to get them to translate the improvement they achieve in the clinic into real life,” Dr. Taub said. “You have to get them to increase the use of the affected arm in real life, and that increased use of the arm can affect brain changes.”

Dr. Taub said giving practical homework assignments, keeping a diary of home activities, such as turning off lights or opening a door, and then problem solving with the therapist afterward is important. If a patient is afraid to hold a cup of coffee with the affected hand out of fear of spilling it, a solution might be to only fill the cup halfway.

Dr. Taub noted, however, that CIMT therapy is expensive ($6,000 at the clinic he runs at UAB) and may not be covered by a person's insurance.



The lead investigator for the two studies, Victor Mark, MD, a neurologist and associate professor in the department of physical medicine and rehabilitation at UAB, said he thought that the findings were noteworthy not only because “this treatment is very effective in improving spontaneous, real-world activity, but this improvement is maintained up to a year out.” He said the findings also show that the neuroplasticity of the brain can be influenced rather quickly, in just two weeks in this case. He noted that the treatment is specifically directed at improving limb use in MS.

“Further research will be needed to determine whether different forms of rehabilitation will benefit other kinds of health concerns of persons with MS, including balance and eyesight,” Dr. Mark said.

The study had limitations. It was very small, including only 20 people, and carried out at a center that specializes in CIMT, so whether the results would be reproducible in other populations of MS patients is not known. The study was not designed to assess how patients were faring otherwise with MS. The therapy was only directed at improving use of the arm and hand most affected by the disease.

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Dr. Wolf, who has collaborated with Dr. Taub, said he was concerned about some of the methodology used in the study, including the fact that the MAL and the WMFT (Wolf Motor Function Test) have been validated for use in assessing stroke patients but not MS. He was also surprised by the large treatment effect that was reported, and would like to see those numbers confirmed by a larger study. He said measuring change in function in MS is complicated because the disease is so variable, with relapses and remission, depending at what point in time you are evaluating someone.

But, Dr. Wolf added, “I think some of the brain information coming from the imaging data is very interesting.”

Carolee Winstein, PhD, PT, professor of biokinesiology and physical therapy at the University of Southern California, told Neurology Today that the new findings on CIMT are important and could help inform how therapy programs are organized for MS patients. She said the “transfer package” components of the program, rather than simply the clinic workouts, seem to be critical to achieving a favorable outcome.



By placing emphasis on out-of-clinic behavior, “it changes how people incorporate their weak side into what they do spontaneously in their natural environment,” she said. Being able to carry out routine tasks helps people maintain independence in the midst of a progressive disease, she said.

Dr. Winstein, who does research on stroke rehabilitation, said the positive changes noted in white matter structure in the study participants who did CIMT should not be considered a reversal of the MS disease process per se, but perhaps a slowing down of motor deterioration, at least in the targeted limb, a sort of neuroprotective effect.

Dr. Winstein said exercise in general is increasingly recognized as a critical component of MS care. “People can do very well with all kinds of exercise.”

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•. Mark VW, Taub E, Uswatte G, et al Phase II randomized controlled trial of constraint-induced movement therapy in multiple sclerosis: Part 1: effects on real-world function Neurorehabil Neural Repair 2018; 32(3): 223–232.
•. Barghi A, Allendorfer JB, Taub E, et al Phase II randomized controlled trial of constraint-induced movement therapy in multiple sclerosis. Part 2: effect on white matter integrity Neurorehabil Neural Repair 2018; 32(3): 233–241.
© 2018 American Academy of Neurology